The role of the hypermetabolic response, observed in patients and experimental animals with extensive thermal injury, will be investigated with special emphasis on its relationship to cellular metabolism. The experiments are designed to establish mechanisms responsible for inhibition of active transport of sodium following burn injury and prolonged negative energy balance. The pathophysiology resulting from inhibition of neutrophil function, abnormal coagulation dynamics, and amino acid deficiency will also be evaluated in burned patients. Finally the role of hormone imbalance in initiating the hypermetabolic response will be assayed. Experimental methods employed include in vitro measurement of sodium flux utilizing Na22, oxygen consumption by neutrophil isolates, fractionation of plasma fibrin split products isolated from burned animals and patients, and amino acid analysis, as well as plasma insulin, glucagon, and catecholamine measurement by radioimmunoassay. Patients and animals are maintained on controlled caloric intakes in order to estimate the effect of negative energy balance on cellular function in patients with major thermal injury.